When the body is repeatedly administered with a drug, such repeated administration may raise an antibody against this drug. Even in the case of recombinant drugs whose amino acid sequences are the same as those of endogenous substances, there is a possibility of raising autoantibodies, some of which may neutralize the original endogenous substances.
For example, in the case of recombinant human erythropoietin (rhEPO), some of the renal failure patients receiving EPO have been found to develop a neutralizing antibody against rhEPO although such cases are very rare, and it has also been reported that this antibody causes anti-EPO antibody-positive pure red cell aplasia (PRCA) as a complication in some patients (Non-patent Document 1).
Since the development of a neutralizing antibody against a drug not only eliminates the efficacy of the drug, but may also induce a new disease, it is important to detect such a neutralizing antibody in an early stage. However, conventional methods used for neutralizing antibody detection are not sufficient for this purpose. By way of example, for measurement of anti-EPO antibody, assays such as ELISA (Enzyme-Linked Immuno Sorbent Assay), RIP (radioactive immunoprecipitation) and bioassay have been used for neutralizing antibody measurement, but it is pointed out that these conventional methods used for neutralizing antibody detection are not sufficient in terms of detection sensitivity and/or complicated procedures (Non-patent Documents 2, 3 and 4). Moreover, antibodies against drugs are produced in very low concentrations in the body, and hence it has been very difficult to determine whether these antibodies are neutralizing antibodies.
For these reasons, once antibody production against a drug has been confirmed, drug administration must be stopped in some cases due to reasons of safety, regardless of whether this antibody has neutralizing activity. Thus, there has been a demand for a highly sensitive and a simple method for detection of neutralizing activity.                Non-patent Document 1: N Engl J. Med. 2002 Feb. 14; 346(7):469-75.        Non-patent Document 2: Journal of Immunological Methods 283 (2003)317-329        Non-patent Document 3: Journal of Immunological Methods 300 (2005)179-191        Non-patent Document 4: Nephrol Dial Transplant (2005)20[Suppl 4]:iv 16-22        